Trial Outcomes & Findings for Pembro+Chemo in Brain Mets (NCT NCT04964960)

NCT ID: NCT04964960

Last Updated: 2025-10-31

Results Overview

Intracranial benefit defined as stable disease, partial response, and complete response

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 3 participants
• Primary outcome timeframe: 6 months (baseline to 6 months)
• Results posted on: 2025-10-31

Participant Flow

Participant milestones

Measure	Pembrolizumab with standard of care chemotherapy treatment Patients will receive 200mg or 400mg of Pembrolizumab (standard of care dosing at the discretion of treating physician) over thirty minutes on day 1 every three or six weeks with standard of care chemotherapy treatment (carboplatin, pemetrexed, paclitaxel, nab-paclitaxel). Pembrolizumab: Pembrolizumab is an immunotherapy that can help fight certain cancers. Nab paclitaxel: Nab-paclitaxel is a taxane derivative that is an albumin-bound paclitaxel nanoparticle formulation that promotes microtubule assembly. Paclitaxel: Paclitaxel is a taxane derivative that promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly, interfering with the late G2 mitotic phase, and inhibiting cell replication. Pemetrexed: Pemetrexed is an antifolate agent that disrupts folate-dependent metabolic processes essential for cell replication. Carboplatin: Carboplatin is a platinum compound alkylating agent which covalently binds to DNA and interferes with the function of DNA by producing interstrand DNA cross-links.
Overall Study STARTED	3
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	Pembrolizumab with standard of care chemotherapy treatment Patients will receive 200mg or 400mg of Pembrolizumab (standard of care dosing at the discretion of treating physician) over thirty minutes on day 1 every three or six weeks with standard of care chemotherapy treatment (carboplatin, pemetrexed, paclitaxel, nab-paclitaxel). Pembrolizumab: Pembrolizumab is an immunotherapy that can help fight certain cancers. Nab paclitaxel: Nab-paclitaxel is a taxane derivative that is an albumin-bound paclitaxel nanoparticle formulation that promotes microtubule assembly. Paclitaxel: Paclitaxel is a taxane derivative that promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly, interfering with the late G2 mitotic phase, and inhibiting cell replication. Pemetrexed: Pemetrexed is an antifolate agent that disrupts folate-dependent metabolic processes essential for cell replication. Carboplatin: Carboplatin is a platinum compound alkylating agent which covalently binds to DNA and interferes with the function of DNA by producing interstrand DNA cross-links.
Overall Study Withdrawal by Subject	1
Overall Study Did not complete cycles	1

Baseline Characteristics

Pembro+Chemo in Brain Mets

Baseline characteristics by cohort

Measure	Pembrolizumab with standard of care chemotherapy treatment n=3 Participants Patients will receive 200mg or 400mg of Pembrolizumab (standard of care dosing at the discretion of treating physician) over thirty minutes on day 1 every three or six weeks with standard of care chemotherapy treatment (carboplatin, pemetrexed, paclitaxel, nab-paclitaxel). Pembrolizumab: Pembrolizumab is an immunotherapy that can help fight certain cancers. Nab paclitaxel: Nab-paclitaxel is a taxane derivative that is an albumin-bound paclitaxel nanoparticle formulation that promotes microtubule assembly. Paclitaxel: Paclitaxel is a taxane derivative that promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly, interfering with the late G2 mitotic phase, and inhibiting cell replication. Pemetrexed: Pemetrexed is an antifolate agent that disrupts folate-dependent metabolic processes essential for cell replication. Carboplatin: Carboplatin is a platinum compound alkylating agent which covalently binds to DNA and interferes with the function of DNA by producing interstrand DNA cross-links.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months (baseline to 6 months)

Population: Number of participants enrolled at 6 month timepoint

Intracranial benefit defined as stable disease, partial response, and complete response

Outcome measures

Measure	Pembrolizumab with standard of care chemotherapy treatment n=2 Participants Patients will receive 200mg or 400mg of Pembrolizumab (standard of care dosing at the discretion of treating physician) over thirty minutes on day 1 every three or six weeks with standard of care chemotherapy treatment (carboplatin, pemetrexed, paclitaxel, nab-paclitaxel). Pembrolizumab: Pembrolizumab is an immunotherapy that can help fight certain cancers. Nab paclitaxel: Nab-paclitaxel is a taxane derivative that is an albumin-bound paclitaxel nanoparticle formulation that promotes microtubule assembly. Paclitaxel: Paclitaxel is a taxane derivative that promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly, interfering with the late G2 mitotic phase, and inhibiting cell replication. Pemetrexed: Pemetrexed is an antifolate agent that disrupts folate-dependent metabolic processes essential for cell replication. Carboplatin: Carboplatin is a platinum compound alkylating agent which covalently binds to DNA and interferes with the function of DNA by producing interstrand DNA cross-links.
Disease Control Rate Stable Disease	0 Participants
Disease Control Rate Complete Response	2 Participants
Disease Control Rate Partial Response	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: participants enrolled at 12 month timepoint

Overall survival at 12-month post-enrollment

Outcome measures

Measure

Pembrolizumab with standard of care chemotherapy treatment n=1 Participants Patients will receive 200mg or 400mg of Pembrolizumab (standard of care dosing at the discretion of treating physician) over thirty minutes on day 1 every three or six weeks with standard of care chemotherapy treatment (carboplatin, pemetrexed, paclitaxel, nab-paclitaxel). Pembrolizumab: Pembrolizumab is an immunotherapy that can help fight certain cancers. Nab paclitaxel: Nab-paclitaxel is a taxane derivative that is an albumin-bound paclitaxel nanoparticle formulation that promotes microtubule assembly. Paclitaxel: Paclitaxel is a taxane derivative that promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly, interfering with the late G2 mitotic phase, and inhibiting cell replication. Pemetrexed: Pemetrexed is an antifolate agent that disrupts folate-dependent metabolic processes essential for cell replication. Carboplatin: Carboplatin is a platinum compound alkylating agent which covalently binds to DNA and interferes with the function of DNA by producing interstrand DNA cross-links.

Number of Participants With Overall Survival at 12-month Post-enrollment

1 Participants

SECONDARY outcome

Timeframe: 12 months (6 months post-enrollment, 12 months post-enrollment)

Population: participants enrolled at 12 months

Extracranial disease control rate (systemic): includes stable disease, partial response, and complete response.

Outcome measures

Measure

Pembrolizumab with standard of care chemotherapy treatment n=1 Participants Patients will receive 200mg or 400mg of Pembrolizumab (standard of care dosing at the discretion of treating physician) over thirty minutes on day 1 every three or six weeks with standard of care chemotherapy treatment (carboplatin, pemetrexed, paclitaxel, nab-paclitaxel). Pembrolizumab: Pembrolizumab is an immunotherapy that can help fight certain cancers. Nab paclitaxel: Nab-paclitaxel is a taxane derivative that is an albumin-bound paclitaxel nanoparticle formulation that promotes microtubule assembly. Paclitaxel: Paclitaxel is a taxane derivative that promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly, interfering with the late G2 mitotic phase, and inhibiting cell replication. Pemetrexed: Pemetrexed is an antifolate agent that disrupts folate-dependent metabolic processes essential for cell replication. Carboplatin: Carboplatin is a platinum compound alkylating agent which covalently binds to DNA and interferes with the function of DNA by producing interstrand DNA cross-links.

Change in Extracranial Disease Control

1 Participants

SECONDARY outcome

Timeframe: 12 months (Baseline and 12 months post enrollment)

Population: participant declined to complete the questionnaire

The FACT-Cog questionnaire was developed to assess perceived cognitive function and impact on quality of life (QOL) in cancer patients. The level of perceived cognitive impairments is measured on a four-point Likert scale (4 = several times a day to 0 = never) FACT-Cog has been widely administered across clinical settings and validated across different cultures and languages. Subjects can complete it in 5 minutes. A higher score indicates a better quality of life/cognitive function.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months (Baseline and 12 months post enrollment)

Population: participant declined to complete the questionnaire

The FACT-Br is a commonly used instrument measuring general quality of life (QOL) that reflects symptoms or problems associated with brain malignancies across 5 subscales. The level of well-being is measured on a four-point Likert scale (4 = very much to 0 = not at all). The measure yields information about total quality of life, as well as information about the dimensions of physical well-being, social/family well-being, emotional well-being, functional well-being, and disease-specific concerns. The score range is 0-200 where a higher score indicated a better quality of life. The FACT-Br is written at the 4th grade reading level, and subjects can complete it in 5-10 minutes.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months (Baseline and 12 months post enrollment)

Population: participant declined to complete the questionnaire

FACIT-F is a short, 13-item, easy to administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four-point Likert scale (4 = not at all fatigued to 0 = very much fatigued) with a score range of 0-52. Subjects can complete the questionnaire in 2-3 minutes and the higher the score, the better the quality of life.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months (Baseline and 12 months post enrollment)

Population: participant declined to complete the questionnaire

Neurocognitive functioning will be evaluated utilizing the Montreal Cognitive Assessment (MoCA). MoCA assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Participants will complete the MoCA (estimated time 10 minutes). The MoCA is scored to obtain an item total, scores can range from 0 to 30 and score of 26 or above is considered normal.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months (Baseline and 12 months post enrollment)

Population: participant declined to complete the questionnaire

Participant performance status will be evaluated utilizing the Eastern Cooperative Oncology Group (ECGO) performance status instrument. Performance status is graded from 0-5 where lower scores indicate better performance/patient daily living abilities.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks (Baseline, 6 weeks after baseline, 6 weeks after prior collection)

PD-1 and several immune-based markers, such as cytotoxic T cells, will be measured and summarized descriptively. Correlations with PD-1 and between markers will be estimated using Pearson or Spearman's correlation coefficient. Exploratory association of these biological markers with DCR will be performed using two-group comparison tests. Adjustment for multiple testing due to several immune-based markers will be considered using Holm's p-value adjustment method.

Outcome measures

Outcome data not reported

Adverse Events

Pembrolizumab with standard of care chemotherapy treatment

Serious events: 0 serious events

Other events: 2 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Pembrolizumab with standard of care chemotherapy treatment n=3 participants at risk Patients will receive 200mg or 400mg of Pembrolizumab (standard of care dosing at the discretion of treating physician) over thirty minutes on day 1 every three or six weeks with standard of care chemotherapy treatment (carboplatin, pemetrexed, paclitaxel, nab-paclitaxel). Pembrolizumab: Pembrolizumab is an immunotherapy that can help fight certain cancers. Nab paclitaxel: Nab-paclitaxel is a taxane derivative that is an albumin-bound paclitaxel nanoparticle formulation that promotes microtubule assembly. Paclitaxel: Paclitaxel is a taxane derivative that promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly, interfering with the late G2 mitotic phase, and inhibiting cell replication. Pemetrexed: Pemetrexed is an antifolate agent that disrupts folate-dependent metabolic processes essential for cell replication. Carboplatin: Carboplatin is a platinum compound alkylating agent which covalently binds to DNA and interferes with the function of DNA by producing interstrand DNA cross-links.
Cardiac disorders Atrial Fibrillation	33.3% 1/3 • 12 months
Cardiac disorders Cardiac disorders - Other	33.3% 1/3 • 12 months
Cardiac disorders Palpitations	33.3% 1/3 • 12 months
Gastrointestinal disorders Nausea	33.3% 1/3 • 12 months
Gastrointestinal disorders Constipation	33.3% 1/3 • 12 months
General disorders Fatigue	66.7% 2/3 • 12 months
General disorders Flu like symptoms	33.3% 1/3 • 12 months
General disorders Other	33.3% 1/3 • 12 months
Infections and infestations Sinusitis	33.3% 1/3 • 12 months
Infections and infestations Tooth infection	33.3% 1/3 • 12 months
Investigations Alanine aminotransferase increased	33.3% 1/3 • 12 months
Investigations Alkaline phosphatase increased	33.3% 1/3 • 12 months
Investigations Aspartate aminotransferase increased	33.3% 1/3 • 12 months
Investigations Creatinine increased	33.3% 1/3 • 12 months
Investigations Lymphocyte count decreased	33.3% 1/3 • 12 months
Investigations Weight gain	33.3% 1/3 • 12 months
Metabolism and nutrition disorders Hypokalemia	33.3% 1/3 • 12 months
Musculoskeletal and connective tissue disorders Pain in extremity	33.3% 1/3 • 12 months
Nervous system disorders Peripheral sensory neuropathy	33.3% 1/3 • 12 months
Nervous system disorders Spasticity	33.3% 1/3 • 12 months

Additional Information

Dr. John Villano

University of Kentucky

Phone: 859-323-0405

Email: jlvillano@uky.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place